title: Role of chemokines and formyl peptides in pneumococcal pneumonia-induced monocyte/macrophage recruitment.
abstract: Host-derived chemoattractant factors are suggested to play crucial roles in leukocyte recruitment elicited by inflammatory stimuli in vitro and in vivo. However, in the case of acute bacterial infections, pathogen-derived chemoattractant factors are also present, and it has not yet been clarified how cross-talk between chemoattractant receptors orchestrates diapedesis of leukocytes in this context of complex chemoattractant arrays. To investigate the role of chemokine (host-derived) and formyl peptide (pathogen-derived) chemoattractants in leukocyte extravasation in life-threatening infectious diseases, we used a mouse model of pneumococcal pneumonia. We found an increase in mRNA expression of eight chemokines (RANTES, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2, IP-10, monocyte chemoattractant protein (MCP)-1, T cell activation 3, and KC) within the lungs during the course of infection. KC and MIP-2 protein expression closely preceded pulmonary neutrophil recruitment, whereas MCP-1 protein production coincided more closely than MIP-1alpha with the kinetics of macrophage infiltration. In situ hybridization of MCP-1 mRNA suggested that MCP-1 expression started at peribronchovascular regions and expanded to alveoli-facing epithelial cells and infiltrated macrophages. Interestingly, administration of a neutralizing Ab against MCP-1, RANTES, or MIP-1alpha alone did not prevent macrophage infiltration into infected alveoli, whereas combination of the three Abs significantly reduced macrophage infiltration without affecting neutrophil recruitment. The use of an antagonist to N-formyl peptides, N-t-Boc-Phe-D-Leu-Phe-D-Leu-Phe, reduced both macrophages and neutrophils significantly. These data demonstrate that a complex chemokine network is activated in response to pulmonary pneumococcal infection, and also suggest an important role for fMLP receptor in monocyte/macrophage recruitment in that model.
authors.affiliation: Centre de Recherche en Infectiologie, Université Laval, Quebec City, Québec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Fillion
authors.forename: N
authors.initials: N
authors.lastname: Ouellet
authors.forename: M
authors.initials: M
authors.lastname: Simard
authors.forename: Y
authors.initials: Y
authors.lastname: Bergeron
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: M G
authors.initials: MG
authors.lastname: Bergeron
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019742:Chemokines, CC / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007106:Immune Sera / Q000502:physiology; D017403:In Situ Hybridization; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology* / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors
chemical_list: D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D007106:Immune Sera; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine