Neutrophil Adhesion Abnormality with Deficient Surface Membrane Proteins (gp 110 and p 98): The Effect of their Antibodies on the Function of Normal Neutrophils

Abstract

ABSTRACT. A sister and brother previously described with neutrophil adhesion defects and a lack of two neutrophi1 membrane proteins, glycoprotein with a molecular weight of 110 K and 115 K, were further studied. Rabbit polyclonal IgG antibodies were raised against neutrophil membrane proteins of approximately 110 K from normal individuals, and absorbed with the siblings' neutrophil membrane proteins. The antibodies thus absorbed reacted with two normal neutrophil membrane proteins, a 110 K glycoprotein and a 9 8 K protein, which were totally deficient in the siblings' neutrophils. The polyclonal antibodies were also reactive with a 9 5 K membrane protein of normal lymphocytes. The protein was missing in the siblings' lymphocytes. Three membrane proteins, Mac-1, LFA-1, and p 150, 9 5 each consisting of a specific a-subunit and a P-subunit common to them, have been reported to be deficient in neutrophils from several patients with a neutrophil adhesion disease. Using monoclonal antibodies to Mac-la, LFA-la, and to the P-subunit, it was deduced that the siblings' neutrophils lacked the above three membrane proteins. The disease in the siblings is thus identical with that previously described. Sodium dodecvl sulfate polyacryla~ide gel ~l e~t r o~h o r e s i s of immunopr~cipitates, formed bv reacting labeled normal neutro~hil membrane -proteins with our polyclonal antibodies, revealed three bands, almost identical with that of immunoprecipitates formed with the anti-P-subunit monoclonal antibody. This finding indicates that the polyclonal antibodies reacted mainly with the P-subunit of the membrane proteins. The presence of the polyclonal antibodies exerted a strong inhibitory effect upon the adhesion of normal neutrophils, an intermediate effect on the chemotaxis, and to a much lesser extent on the phagocytosis. (Pediatr Res 20: 361-366,1986) Abbreviations gp 110, glycoprotein with a molecular weight of 110 K gp 115, glycoprotein with a molecular weight of 115 K p 98, protein with a molecular weight of 9 8 K PBS, phosphate-buffered saline SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresisWe have described a sister and brother who suffered from recurrent bacterial infections and whose neutrophils exhibited impaired adhesion, chemotaxis, and phagocytosis (I, 2). Their neutrophils lacked two membrane glycoproteins: one with a molecular weight of 110 K (gp 110) present on the cell surface, and the other with a molecular weight of 1 15 K (gp 1 15) possibly situated in the intracellular apparatuses. Their parents, both healthy, showed a reduced rate of neutrophil adhesion and reduced levels of the two glycoproteins. The disease was thus inherited in an autosomal recessive fashion. Scanning electron microscopy of the neutrophils from the brother attached on a glass surface revealed a considerable reduction of the pseudopods. On the other hand, his neutrophils in suspension were morphologically normal, a finding indicating that the cytoskeleton of the neutrophils was functionally intact (2). Several rec...

LEUKOCYTE ADHESION DEFICIENCY: An Inherited Defect in the Mac-1, LFA-1, and p150,95 Glycoproteins

“…The affec ted son married a heterozygote, and the couple bore an affected son and daughter and two heterozygous daughters. These fi ndings, together with an equal number of male and f emale patients (Table 1), a frequent history of consanguineous marriages (4, 22,23,31,39,41), and the presence in many families of both male and female patients (4, 26,29,32,37,38,40), strongly suggest that LAD is inherited as a recessive defect on an auto somal chromosome. In one family, X-linked inheritance was found (12, 13).…”

“…Other leukocyte cell types are also defi cient, including peripheral blood lymphocytes and cultured cytolytic T-Iymphocytes, mitogen-stimulated T-Iymphocytes, and EBV transformed B-lymphocyte cell lines (3, 8, 13). We have examined ten patients with MAbs specific for all four subunits (4), and other labs have reported studies on MAbs specific for two of the ex subunits and/or the common fJ subunit (13,20,23,27,30,32). There is thus far no example of a selective deficiency in only one or two of the exfJ complexes; a defi ciency in all three appears to be a general fi nding.…”

Leukocyte Adhesion Molecules Deficiency: Its Structural Basis, Pathophysiology and Implications for Modulating the Inflammatory Response

“…Len-CAM (CD 11/CD 18) deficiency is a rare disease (approximately 60 patients have so far been described worldwide) which commonly presents in the pediatric age group and affects males and females equally {Dana & Amaout 1988). The bulk of the patients are Caucasians (with different ethnic background) and 2 Japanese patients have been reported {Fujita et al 1986). In the majority of cases, the mode of inheritance is on an autosomal recessive basis.…”