Role of E- and P-selectin in migration of monocytes and polymorphonuclear leucocytes to cytokine and chemoattractant-induced cutaneous inflammation in the rat

Immunology. 1997 Oct;92(2):290-9. doi: 10.1046/j.1365-2567.1997.d01-2314.x.

Abstract

The contribution of E- and P-selectin in the rat to the migration of polymorphonuclear leucocytes (PMNL) and monocytes to acute dermal inflammation induced by a chemoattractant (C5ades Arg) or endothelial cell activating agents [lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), alpha-thrombin and interferon-gamma] administered intradermally was investigated. Migration was quantitated using radiolabelled blood PMNL and monocytes and new, function-blocking monoclonal antibodies (mAbs) to rat E- and P-selectin were employed. Monocyte migration to inflamed skin was partially inhibited (40-75%) by P-selectin mAb with all stimuli tested, but not by anti-E-selectin. PMNL migration in response to all stimuli was also inhibited (50-75%) by blocking P-selectin, but in contrast to monocytes, PMNL accumulation was partially inhibited by mAb to E-selectin in alpha-thrombin and TNF-alpha lesions. When P-selectin was blocked by mAb, mAb to E-selectin significantly inhibited further (by 70-90%) both PMNL and monocyte accumulation in all lesions, indicating that both P- and E-selectin contribute to the migration of these leucocytes. Blocking L-selectin in addition to P- and E-selectin, had no effect on the remaining migration. Thus, optimal PMNL and monocyte migration to chemotactic factor- and cytokine-induced skin inflammation is P-selectin dependent. E-selectin becomes important, in most conditions used here, when P-selectin mediated recruitment is not operative. A selectin independent pathway likely mediates up to 20% of PMNL and monocyte migration to acute inflammation, at least in skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Chemotactic Factors / immunology
  • Chemotaxis, Leukocyte / immunology*
  • Dermatitis / etiology
  • Dermatitis / immunology*
  • Dermatitis / pathology
  • E-Selectin / immunology
  • L-Selectin / immunology
  • Male
  • Monocytes / immunology*
  • Neutrophils / immunology*
  • P-Selectin / immunology
  • Rats
  • Rats, Inbred Lew
  • Selectins / immunology*

Substances

  • Antibodies, Monoclonal
  • Chemotactic Factors
  • E-Selectin
  • P-Selectin
  • Selectins
  • L-Selectin