In vivo E-selectin upregulation correlates early with infiltration of PMN, later with PBL entry: MAbs block both

Am J Physiol. 1996 Jan;270(1 Pt 2):H183-93. doi: 10.1152/ajpheart.1996.270.1.H183.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Movement / drug effects
  • Drug Eruptions / etiology
  • E-Selectin / immunology
  • E-Selectin / metabolism*
  • Humans
  • Interleukin-1 / pharmacology
  • Kinetics
  • Lymphocytes / physiology*
  • Neutrophils / physiology*
  • Phytohemagglutinins / pharmacology
  • Recombinant Proteins
  • Skin / drug effects
  • Swine
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antibodies, Monoclonal
  • E-Selectin
  • Interleukin-1
  • Phytohemagglutinins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha