In vivo E-selectin upregulation correlates early with infiltration of PMN, later with PBL entry: MAbs block both.
The endothelial molecule E-selectin binds most leukocyte subsets in vitro. Yet its role in regulating the very different kinetics of inflammatory infiltration of different leukocyte subsets in vivo is unclear. The kinetics of E-selectin upregulation and polymorphonuclear leukocyte (PMN) and blood lymphocyte (PBL) localization in inflammation induced by interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), phytohemagglutinin (PHA), and phorbol myristate acetate (PMA) were investigated in a well-established inbred pig trafficking model. They differed markedly both for these three labeled indicators of inflammation and in each of the four inflammatory processes. In each, E-selectin upregulation correlated with early PMN entry and later with PBL infiltration but was more protracted than both. The importance of E-selectin was confirmed by marked inhibition of PMN and PBL entry (up to > 60%) by F(ab')2 anti-E-selectin. Involvement of other molecules was illustrated by similar or greater inhibition with anti-CD18 F(ab')2. We conclude that, like CD18, E-selectin is necessary for most PMN and PBL infiltration but alone is insufficient, consistent with the involvement of several alternative multistep molecular mechanisms in this entry.
Binns
R M
RM
Department of Immunology, Babraham Institute, Cambridge, United Kingdom.
Licence
S T
ST
Harrison
A A
AA
Keelan
E T
ET
Robinson
M K
MK
Haskard
D O
DO
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D003875:Drug Eruptions / Q000209:etiology; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008214:Lymphocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins; D012867:Skin / Q000187:drug effects; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D007375:Interleukin-1; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha