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Leukocyte adhesion deficiency

INTRODUCTION

Leukocyte trafficking from the bloodstream to tissue is important for the continuous surveillance of foreign antigens, as well as for rapid leukocyte accumulation at sites of inflammatory response or tissue injury. Leukocyte emigration to sites of inflammation is a dynamic process, involving multiple steps in an adhesion cascade. Various adhesion molecules are expressed on both resting and stimulated endothelial cells and leukocytes.

Defects in a number of these adhesion molecules result in recognized clinical syndromes. Three Leukocyte Adhesion Deficiency (LAD) syndromes have been delineated and a fourth category of newly-described defects will be reviewed [1]:

  • LAD I, in which the beta 2-integrin family is deficient or defective
  • LAD II, in which the fucosylated carbohydrate ligands for selectins are absent
  • LAD III, in which activation of all beta–integrins (1, 2, and 3) is defective
  • Other defects of neutrophil adhesion

Issues related to the LAD syndromes will be reviewed here. Other neutrophil disorders, and the process of leukocyte-endothelial adhesion during inflammation are discussed separately. (See "Primary disorders of phagocytic function: An overview" and "Leukocyte-endothelial adhesion in the pathogenesis of inflammation".)

OVERVIEW OF LEUKOCYTE MIGRATION

Inflammation is characterized histologically by the accumulation of leukocytes at the involved site due to the directional migration of circulating leukocytes. Migration out of the vasculature is first initiated by contact between the leukocyte and the inflamed vascular endothelium. Both the vascular endothelium and leukocytes actively mediate this adhesive interaction, which will be reviewed briefly here. A detailed review of the adhesion cascade is found separately. (See "Leukocyte-endothelial adhesion in the pathogenesis of inflammation".)
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