Papers by Cecilia Garlanda
Frontiers in Immunology, Apr 12, 2019
The first line of defense in innate immunity is provided by cellular and humoral mediators. Pentr... more The first line of defense in innate immunity is provided by cellular and humoral mediators. Pentraxins are a superfamily of phylogenetically conserved humoral mediators of innate immunity. PTX3, the first long pentraxin identified, is a soluble pattern recognition molecule rapidly produced by several cell types in response to primary pro-inflammatory signals and microbial recognition. PTX3 acts as an important mediator of innate immunity against pathogens of fungal, bacterial and viral origin, and as a regulator of inflammation, by modulating complement activation and cell extravasation, and facilitating pathogen recognition by myeloid cells. In sepsis, PTX3 plasma levels are associated with severity of the condition, patient survival, and response to therapy. In combination with other established biomarkers, PTX3 could improve stratification of sepsis patients and thus, complement the system of classification and monitoring of this disease.
Frontiers in Immunology, Oct 28, 2022
Background: PTX3 is an important mediator of inflammation and innate immunity. We aimed at assess... more Background: PTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19. Methods: Levels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to inhospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method. Results: Upon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P<0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P<0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median [
Chronic inflammation, including that driven by autoimmunity, is associated with the development o... more Chronic inflammation, including that driven by autoimmunity, is associated with the development of B-cell lymphomas. IL1R8 is a regulatory receptor belonging to the IL1R family, which negatively regulates NF-kB activation following stimulation of IL1R or Toll-like receptor family members. IL1R8 deficiency is associated with the development of severe autoimmune lupus-like disease in lpr mice. We herein investigated whether concomitant exacerbated inflammation and autoimmunity caused by the deficiency of IL1R8 could recapitulate autoimmunity-associated lymphomagenesis. We thus monitored B-cell lymphoma devel-opment during the aging of IL1R8-deficient lpr mice, observing an increased lymphoid cell expansion that evolved to diffuse large B-cell lymphoma (DLBCL). Molecular and gene-expression analyses showed that the NF-kB pathway was constitutively activated in Il1r8 À/À /lpr B splenocytes. In human DLBCL, IL1R8 had reduced expression compared with normal B cells, and higher IL1R8 expression was associated with a better outcome. Thus, IL1R8 silencing is associated with increased lymphoproliferation and transformation in the pathogenesis of B-cell lymphomas associated with autoimmunity.
Clinical & Experimental Allergy Reviews, 2004
SummaryPentraxin 3 (PTX3), the first long pentraxin identified, is characterized by a C‐terminal ... more SummaryPentraxin 3 (PTX3), the first long pentraxin identified, is characterized by a C‐terminal pentraxin like domain, showing sequence similarity to C‐reactive protein and serum amyloid P component, coupled with a N‐terminal unrelated portion. PTX3 is made by diverse cell types, including endothelial cells, macrophages and dendritic cells, in response to proinflammatory signals such as interleukin 1, tumor necrosis factor and lipopolysaccharide. It binds different ligands, including Clq, apoptotic cells and microbial mojcties. PTX3 levels are <2 ng/mL in normal subjects but increase in a number of pathological conditions such as autoimmune, infectious and degenerative disorders. Evidence from clinical studies and genetically modified animals suggests that PTX3 plays a role in inflammatory reactions as well as in the regulation of innate resistance to pathogens and female fertility. The results obtained so far indicate that PTX3 is a soluble pattern recognition receptor which pl...
The Journal of Immunology, 2009
Atherosclerosis Supplements, 2003
1SY02 Immunity and Inflammation in Atherosclerosis scription of downstream target genes. In the e... more 1SY02 Immunity and Inflammation in Atherosclerosis scription of downstream target genes. In the enterohepatic system, these target genes include cytochrome P450s and other enzymes that catabolize the lipid, intracellular binding proteins that buffer the lipid in cells, and ATP-binding cassette transporters that move lipids out of cells. Our newest studies have shown that these lipid sensing receptors also play key roles in orchestrating the transport, storage, and metabolism of cholesterol, triglycerides, and free fatty acids in peripheral tissues, such kidney, muscle, adipose, lung, spleen, the immune system, and the central nervous system. The focus of our most recent studies in these tissues has been on the LXRs. Remarkably, in addition to maintaining cholesterol homeostasis, we have now shown that the LXRs are required for the body to respond properly to dietary fat. These studies point to a unique mechanism of action that involves a complex cross-talk with several metabolic pathways, and other nuclear receptors.
Atherosclerosis Supplements, 2010
The CD40-CD40 ligand (CD40L) signaling axis plays an important role in immunological pathways. Co... more The CD40-CD40 ligand (CD40L) signaling axis plays an important role in immunological pathways. Consequently, this dyad is involved in a plethora of chronic inflammatory diseases, including atherosclerosis.
Developments in biological standardization, 1999
Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment
The recruitment of leukocytes from the blood compartment constitutes a multistep process which in... more The recruitment of leukocytes from the blood compartment constitutes a multistep process which involves primary and secondary inflammatory cytokines, as well as adhesion molecules expressed on leukocytes and endothelial cells. The properties of the interleukin (IL)-1 system and of chemokines, as well as their interplay, are analysed. These mediators offer new paradigms to understand diverse pathologies, and provide tools and targets for the development of novel therapeutic strategies.
Cancer Therapy, 1993
Macrophages are a major component of the lymphoreticular infiltrate of tumors. Tumor-derived cyto... more Macrophages are a major component of the lymphoreticular infiltrate of tumors. Tumor-derived cytokines play an important role in the regulation of the recruitment and function of tumor-associated macrophages (TAM). TAM have pleiotropic functions that influence various aspects of the immunobiology of neoplastic tissues including vascularization, stroma formation and dissolution, and growth rate. These cells, strategically located at the interface between tumor and host, have the potential to destroy neoplastic tissues and hence are a target for therapeutic Intervention. Recent clinical results in ovarian cancer encourage efforts along this line.
European cytokine network
TIR8, also known as single Ig IL-1R-related molecule (SIGIRR), is a member of the IL-1 receptor f... more TIR8, also known as single Ig IL-1R-related molecule (SIGIRR), is a member of the IL-1 receptor family. The present study was designed to investigate the expression and function of TIR8. TIR8 was mainly expressed in mouse and human epithelial tissues such as kidney, lung and gut. Resting and activated T and B lymphocytes and monocytes-macrophages expressed little or no TIR8, with the exception of the mouse GG2EE macrophage line. In the kidney, the organ with highest mRNA levels, TIR8 expression was confined to epithelial cells and, in situ, to tubular epithelium. A variety of signals failed to regulate TIR8 expression, but LPS reduced TIR8 mRNA transcripts. An NF-kB driven reporter system was used to investigate the function of TIR8. TIR8 did not activate NF-kB expression alone or in concert with IL-1R1. In contrast, TIR8 inhibited signaling from the IL-1R complex. Inhibition required the intracellular portion of TIR8 but the extracellular domain was dispensable for blocking activit...
Atherosclerosis
137 7 Pentraxins in Vascular Pathology: The Role of PTX 3 Alberto Mantovani, Cecilia Garlanda, Ba... more 137 7 Pentraxins in Vascular Pathology: The Role of PTX 3 Alberto Mantovani, Cecilia Garlanda, Barbara Bottazzi, Fabiola Molla, and Roberto Latini ... like receptor s (TLR s) by outer membrane protein A or peptidoglycan (TLR2), poly (I):(C)(TLR3), LPS, or Candida (TLR4) and ...
Progress in Inflammation Research
Veterinary Immunology and Immunopathology, 2009
Journal of the Society for Gynecologic Investigation, 2006
Pentraxin-3 (PTX3) is a long pentraxin that plays a key role in female fertility as a structural ... more Pentraxin-3 (PTX3) is a long pentraxin that plays a key role in female fertility as a structural and essential constituent of the cumulus oophorus extracellular matrix. Despite considerable evidence supporting this role of PTX3 in mice, data in humans are scanty. The aim of the present study was (1) to evaluate follicular fluid concentrations of PTX3; (2) to test the hypothesis that levels of the molecule correlate with oocyte characteristics (corona radiata, aspect of the cumulus, nuclear maturity, and fertilization); and (3) to evaluate the possibility that peripheral concentration of PTX3 may be of clinical help in monitoring ovarian hyperstimulation. ELISA was used to determine PTX3 concentration. Levels of PTX3 were tested in 96 follicles. The mean +/- SD and the median (interquartile range) were 17.9 +/- 18.3 and 12.1 (6.5-23.6) ng/mL, respectively. Levels of the molecule did not appear to be normally distributed. At the day of ovum pick-up, levels of PTX3 were 6.3-fold higher in follicular fluid than in peripheral blood (95% CI, 3.6-9.0). No statistically significant difference emerged linking follicular fluid concentration of PTX3 and oocyte quality. In a series of ten women, plasma concentration of PTX3 did not vary during ovarian hyperstimulation, resulting in levels of 1.0 +/- 0.5 at the 3rd day of the menstrual cycle and 1.0 +/- 0.6 ng/mL at the day of oocyte retrieval. Results from the present study support the following conclusions: (1) elevated levels of soluble PTX3 can be found in follicular fluid; (2) follicular fluid concentration of PTX3 cannot by used as a marker of oocyte quality; and (3) plasma concentration of the molecule is not influenced by ovarian hyperstimulation.
Nature Immunology, 2013
Platelets and phagocytes engage in bidirectional interaction in innate immunity and inflammation.... more Platelets and phagocytes engage in bidirectional interaction in innate immunity and inflammation. Kupffer cell–platelet cooperation results in the rapid encasement of blood-borne bacteria and host protection.
Intensive Care Medicine, 2010
Current Opinion in Genetics & Development, 2008
Chronic and persistent inflammation contributes to cancer development and can predispose to carci... more Chronic and persistent inflammation contributes to cancer development and can predispose to carcinogenesis. Infectiondriven inflammations are involved in the pathogenesis of approximately 15-20% of human tumors. However, even tumors that are not epidemiologically linked to pathogens are characterized by the presence of an inflammatory component in their microenvironment. Hallmarks of cancer-associated inflammation include the presence of infiltrating leukocytes, cytokines, chemokines, growth factors, lipid messengers, and matrix-degrading enzymes. Schematically, two interrelated pathways link inflammation and cancer: (1) genetic events leading to neoplastic transformation promote the construction of an inflammatory milieu; (2) tumor-infiltrating leukocytes, in particular macrophages, are prime regulators of cancer inflammation. Thus, an intrinsic pathway of inflammation (driven in tumor cells), as well as an extrinsic pathway (in tumorinfiltrating leukocytes) have been described and both contribute to tumor progression.
Cardiovascular Pathology, 2011
The long pentraxin 3 is involved in innate resistance to pathogens, controlling inflammation and ... more The long pentraxin 3 is involved in innate resistance to pathogens, controlling inflammation and extracellular matrix remodeling. Moreover, pentraxin 3 plays a nonredundant role in the regulation of cardiac tissue damage in mice and, recently, it has been proposed as a new candidate marker for acute and chronic heart diseases. However, the actual localization and cellular sources of pentraxin 3 in ischemic and infectious cardiac pathology have not been carefully defined. In this study, using immunohistochemistry, we analyzed pentraxin 3 expression in the heart tissues of patients with acute myocardial infarction at different time points after the ischemic event. In addition, we studied the heart tissues of patients with infectious myocarditis (fungi, bacteria, and protozoa) and patients who died of noncardiac events with normal heart histology. In acute myocardial infarction cases, we observed pentraxin 3 localized within and around ischemic lesions. On the contrary, no pentraxin 3 was observed in normal heart areas. In early ischemic lesions, pentraxin 3 was localized primarily in granulocytes; in more advanced acute myocardial infarction, pentraxin 3 positivity was found in the interstitium and in the cytoplasm of macrophages and the endothelium, whereas most granulocytes did not express pentraxin 3, presumably as a consequence of degranulation. In infectious myocarditis, pentraxin 3 was present and localized within and around histological lesions, associated with macrophage, endothelial cell, and, more rarely, myocardiocyte and granulocyte positivities. As observed in acute myocardial infarction patients, no pentraxin 3 staining was found in normal heart areas. Thus, neutrophils are an early source of pentraxin 3 in acute myocardial infarction and presumably other inflammatory heart disorders. Subsequently, in acute myocardial infarction and infectious myocarditis, pentraxin 3 is produced by macrophages, the endothelium, and, to a lesser extent, myocardiocytes, and localized in the interstitium.
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Papers by Cecilia Garlanda