Stimulus-dependent requirement for granulocyte-macrophage colony-stimulating factor in inflammation.
Data from several inflammation/autoimmunity models indicate that GM-CSF can be a key inflammatory mediator. Convenient models in readily accessible tissues are needed to enable the GM-CSF-dependent cellular responses to be elaborated. In this study, we show that, in contrast to the response to the commonly used i.p. irritant, thioglycolate medium, an Ag-specific methylated BSA-induced peritonitis in GM-CSF(-/-) mice was severely compromised. The reduced response in the latter peritonitis model was characterized by fewer neutrophils and macrophages, as well as by deficiencies in the properties of the remaining macrophages, namely size and granularity, phagocytosis, allogeneic T cell triggering, and proinflammatory cytokine production. B1 lymphocytes were more evident in the GM-CSF(-/-) Ag-specific exudates, indicating perhaps that GM-CSF can act on a common macrophage-B1 lymphocyte precursor in the inflamed peritoneum. We propose that these findings contribute to our understanding of how GM-CSF acts as a proinflammatory cytokine in many chronic inflammatory/autoimmune diseases. Of general significance, the findings also indicate that the nature of the stimulus is quite critical in determining whether a particular inflammatory mediator, such as GM-CSF, plays a role in an ensuing inflammatory reaction.
Cook
Andrew D
AD
Arthritis and Inflammation Research Centre, Department of Medicine, Royal Melbourne Hospital, and Cooperative Research Centre for Chronic Inflammatory Diseases, University of Melbourne, Victoria, Australia. adcook@unimelb.edu.au
Braine
Emma L
EL
Hamilton
John A
JA
D000818:Animals; D001202:Ascitic Fluid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D016023:Integrins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D007959:Lymphocyte Culture Test, Mixed; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013864:Thioglycolates / Q000008:administration & dosage
D016207:Cytokines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D016023:Integrins; D013864:Thioglycolates; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor