Polymorphonuclear leucocyte migration through human dermal fibroblast monolayers is dependent on both beta 2-integrin (CD11/CD18) and beta 1-integrin (CD29) mechanisms

Immunology. 1995 Jul;85(3):485-94.

Abstract

Accumulation of leucocytes in inflammation involves their migration through vascular endothelium and then in the connective tissue. We investigated human polymorphonuclear leucocyte (PMNL) migration through a biological barrier of human dermal fibroblasts grown on microporous filters, as a model of PMNL migration in the connective tissue. PMNL did not migrate through a fibroblast monolayer unless a chemotactic factor, e.g. C5a, interleukin-8 (IL-8) or zymosan-activated plasma (ZAP; C5adesArg), was added. This migration was partially inhibited (35-70%, depending on the stimulus) by treatment of PMNL with monoclonal antibody (mAb) to CD18 (beta 2-integrins). Most of the CD18-independent migration was inhibited by mAb to beta 1-integrins (CD29). Inhibition by mAb to beta 1 was observed when the PMNL, but not the fibroblasts, were treated with mAb. The role of beta 1-integrins in PMNL transfibroblast migration was detectable only when the function of the CD11-CD18 complex was blocked, because mAb to beta 1-integrin alone had no significant effect on PMNL migration. Migration induced by C5a was more CD18-independent compared to IL-8 or C5adesArg. The CD18-independent migration was also inhibited by mAb to the beta 1-integrin subunits alpha 5 (of very late antigens-5; VLA-5) and alpha 6 (of VLA-6). Treatment of the fibroblasts (4 hr) with tumour necrosis factor-alpha (TNF-alpha) or IL-1 alpha enhanced C5a-induced PMNL transfibroblast migration and increased the proportion of migration utilizing the CD11-CD18 mechanism. However, TNF-alpha treatment had no effect on the degree of beta 1-integrin-dependent migration. These findings suggest that in response to the chemotactic factors C5a, IL-8 and C5adesArg, PMNL migration in the connective tissue is mediated by both CD11-CD18 (beta 2) and beta 1-integrins on the PMNL. The VLA-5 and VLA-6 members of beta 1-integrins are involved in this process. This is in contrast to PMNL migration across endothelium in this system, which is virtually all CD18 dependent with no significant role for beta 1-integrins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD18 Antigens / immunology*
  • Cell Movement / immunology
  • Cells, Cultured
  • Chemotactic Factors / immunology
  • Child
  • Complement C5a / immunology
  • Cytokines / immunology
  • Fibroblasts
  • Humans
  • Infant, Newborn
  • Integrin beta1 / immunology*
  • Interleukin-1 / immunology
  • Neutrophils / immunology*
  • Neutrophils / physiology
  • Receptors, Very Late Antigen / immunology
  • Skin / immunology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • CD18 Antigens
  • Chemotactic Factors
  • Cytokines
  • Integrin beta1
  • Interleukin-1
  • Receptors, Very Late Antigen
  • Tumor Necrosis Factor-alpha
  • Complement C5a