Reduction in inflammation following blockade of CD18 or CD29 adhesive pathways during the acute phase of a spirochetal-induced colitis in mice.
Colitis develops in mice infected with Brachyspira (Serpulina) hyodysenteriae. Numerous granulocytes (PMNs) are evident in cecal tissue sections 24-48 h post-infection. The role of PMNs was assessed by utilizing monoclonal antibodies specific for CD18 or CD29 to block PMN recruitment. Macroscopic lesions were less severe in mice treated with either monoclonal antibody compared to lesions observed in isotype control-treated mice. While these monoclonal antibodies may inhibit extravasation of other leukocytes, the central role of PMNs was further demonstrated in that colitis was reduced following neutrophil depletion. There was less edema and epithelial erosions in ceca of mice receiving anti-Ly6G, -CD18 or -CD29 monoclonal antibody compared to mice receiving the control. Moreover, there was a significant reduction in PMN infiltration in tissues of mice treated with anti-CD18. The reduction in infiltrating PMNs did not result from downregulation of neutrophil chemoattractant MIP-2 expression in anti-CD18-treated mice. In contrast, PMN recruitment into the cecum was apparently CD29-independent. It is noteworthy that the number of PMNs observed in anti-CD18-treated mice was significantly higher than observed in non-infected mice. The data provide evidence for a threshold number of PMNs necessary for lesion development and indicate that CD18, but not CD29, adhesive pathways are crucial for PMN recruitment in bacterial colitis.
Sacco
R E
RE
Veterinary Medical Research Institute, Iowa State University, Ames, IA, USA. rsacco@nadc.ars.usda.gov
Hutto
D L
DL
Waters
W R
WR
Xiasong
L
L
Kehrli
M E
ME
Zuckermann
F A
FA
Wannemuehler
M J
MJ
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001422:Bacterial Adhesion / Q000187:drug effects; D018821:CD18 Antigens / Q000032:analysis*; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D054426:Chemokine CXCL2; D003092:Colitis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D006098:Granulocytes / Q000502:physiology; D019012:Integrin beta1 / Q000032:analysis*; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D015846:Monokines / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013144:Spirochaetales / Q000472:pathogenicity*; D013145:Spirochaetales Infections / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D054426:Chemokine CXCL2; D019012:Integrin beta1; D015846:Monokines; D012333:RNA, Messenger