Defects neutrophil adhesion

Primary defects in neutrophils expose individuals to recurring infections. These defects may be due to a variety of causes such as neutrophil adhesion defects, defects in phagocyte function, and other causes. 

Table 7 reiterates the causes and effects of neutrophil adhesion defects. 

Leukocyte Adhesion Deficiency Type 2. Patients with this condition have a defect in the transport or production of the carrier molecule for the carbohydrate L-fucose (guanosine disphosphate L-fucose). The lack of fucose affects the ability of neutrophils to interact with ligands on endothelial cells such as P-selectins and E-selectins (81). Patients are susceptible to recurrent infections similar to those afflicting patients with type 1 leukocyte adhesion deficiency, have periodontal problems, and, in addition, may exhibit growth retardation and neurologic defects. Treatment with oral fucose has been known to be effective in reducing the frequency of infections (80). 

The cytoplasmic domain of P-selectin contains signals that mediate its rapid en-docytosis in clathrin-coated pits. Interactions of the cytoplasmic domain of P-selectin with these structures were found to enhance its adhesive function under flow [47]. Transfected CHO cells were prepared that express wild-type P-selectin or P-selectin constructs with substitutions or deletions in the cytoplasmic domain that either increase or decrease its internalization rate. Under flow, neutrophils tether equivalently to all constructs when expressed at matched densities. However, neutrophils roll on the internalization-competent constructs with greater adhesive strength, at slower velocities, and with more uniform motion. Confocal immunofluorescence microscopy demonstrates colocalization of a-adaptin, a component of clathrin-coated pits, with wild-type P-selectin but not with internalization-defective P-selectin lacking the cytoplasmic domain. Thus, interactions of P-selectin with clathrin-coated pits provide an alternative to cytoskeletal interactions to enhance adhesive function. The association of P-selectin with clathrin-coated pits may delay dissociation of P-selectin-PSGL-1 bonds and/or prevent forced extraction of P-selectin from the membrane. 

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