The common acute lymphoblastic leukemia antigen (CD10)--emancipation from a functional enigma.
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Antigens, Differentiation↗
Biomedical subjects
R T McCormack
Publications and source records attributed to R T McCormack.
Decreased expression of the common acute lymphoblastic leukaemia antigen (CALLA/CD10) on neutrophils from patients with thermal injury.
The common acute lymphoblastic leukaemia antigen (CALLA/CD10) is a normal component of the circulating neutrophil cell surface membrane. In order to examine the potential functional significance of CALLA/CD10 we analysed the expression of this molecule on neutrophils isolated from thermal injury patients, since these patients have a well-documented constellation of neutrophil defects affecting their microbicidal functions. Expression of neutrophil CALLA/CD10 was monitored by indirect immunofluorescence and flow cytometry. We observed that CALLA/CD10 expression was quantitatively reduced on burn patient neutrophils, compared to healthy donors (P less than 0.001). In contrast, burn patient neutrophils expressed normal levels of class I HLA molecules and the C3bi receptor. Reduced expression of CALLA/CD10 was not associated with neutrophil activation or exposure to plasma 'factor(s)' in vivo. Analysis of normal bone marrow neutrophils by cell sorting indicated that expression of CALLA/CD10 occurs late in neutrophil maturation, since 25% of polymorphonucleated bone marrow neutrophils did not express cell surface CALLA/CD10. Attempts to examine the chemotactic responses of CALLA/CD10 positive and negative neutrophils from burn patients were hampered by previous exposure of these cells to chemoattractants in vivo. Collectively, our findings suggest that burn patient peripheral blood neutrophils may be deficient in CALLA/CD10 due to insufficient maturation time in the bone marrow following thermal injury.
Adult↗
Identification and characterization of a unique subpopulation (CALLA/CD10/negative) of human neutrophils manifesting a heightened chemotactic response to activated complement.
We have previously demonstrated that human neutrophils synthesize the common acute lymphoblastic leukemia antigen (CALLA/CD10). To determine whether CALLA/CD10-positive and -negative neutrophils have similar or distinct functional attributes, we sorted normal peripheral blood neutrophils for CALLA/CD10 expression and compared their chemotactic ability. Surprisingly, the low-frequency (approximately 5%), CALLA/CD10-negative neutrophils displayed a dramatically heightened chemotactic response to activated complement (C') that was (a) specific for C', (b) not observed with other minor subpopulations of neutrophils, (c) not due to previous activation in vivo or in vitro, and (d) apparently not due to an increase in C5a receptors. These results underscore the concept of neutrophil heterogeneity and prompt the hypothesis that CALLA/CD10-negative neutrophils may participate in an inflammatory response to trauma involving complement activation.
Antibodies, Monoclonal↗
Structure/function studies of the common acute lymphoblastic leukemia antigen (CALLA/CD10) expressed on human neutrophils.
The common acute lymphoblastic leukemia antigen (CALLA/CD10) is a nonintegral membrane glycoprotein expressed on normal and neoplastic cells of hematopoietic and nonhematopoietic origin. We have undertaken a series of experiments to examine 1) the structural homology between leukemia cell and neutrophil CALLA/CD10 and 2) the putative function CALLA/CD10 subserves to human neutrophils. Biosynthetic labeling, peptide mapping, and two-dimensional gel electrophoresis indicate that neutrophils synthesize and express a CALLA/CD10 molecule that is similar, but not identical, to leukemic cell CALLA/CD10. The level of CALLA/CD10 expression is similar on the two cell populations, and neutrophil CALLA/CD10 (like its leukemic cell counterpart) undergoes antigenic modulation. Finally, we report that neutrophil cell surface-bound anti-CALLA/CD10 monoclonal antibodies inhibit the chemotactic response to both N-Formyl-methionyl-leucyl-phenylalanine (F-mlp) and zymosan-activated sera (ZAS), but had no inhibitory effect on random migration, degranulation, or aggregation. The anti-class I monoclonal antibody W6/32 exerted a similar effect on chemotaxis. We conclude that CALLA/CD10 has no clearly defined role in neutrophil function but may play a role in some distal event in chemotaxis.
Antibodies, Monoclonal↗
p24 and p26, structurally related cell surface molecules identified by monoclonal antibody BA-2.
This paper describes additional structural analyses of the p24 cell surface molecule recognized by monoclonal antibody BA-2. Since BA-2 is broadly reactive with a variety of normal and malignant lymphohematopoietic and nonlymphohematopoietic cells, we examined the structure of p24 expressed on different cell types. Tryptic peptide mapping and 2-dimensional gel electrophoresis of p24 isolated from colon carcinoma cells, fresh leukemic cells, leukemic cell lines, and activated T-cells indicated that p24 exhibits no structural polymorphism within the cells examined. As has recently been demonstrated with several other cell surface molecules, p24 is shown to possess a covalently-attached fatty acid, based on the incorporation of [3H]palmitate. We have also identified an additional protein, designated p26, that is coprecipitated with p24. The p26 molecule is not disulfide-linked to p24, and can be immunoprecipitated from a variety of 125I- or [35S]methionine-labeled cells. V8 protease peptide mapping indicated that p24 and p26 are structurally homologous. Pulse-chase analysis using [35S]methionine and digestion with endoglycosidase-F indicated that p24 and p26 are probably derived from a p23 precursor, but no precursor-product relationship exists between p24 and p26. Based on this data we propose that p24 and p26 are most likely differentially-processed protein products of the same gene.
Antibodies, Monoclonal↗
Neutrophil function in lymphoreticular malignancy.
Neutrophil chemotaxis, phagocytosis, and metabolic stimulation were studied in 25 patients with untreated lymphoreticular malignancies, 8 patients with untreated carcinomas, and 8 patients undergoing therapy for lymphoreticular tumors. Phagocytic activity and metabolic stimulation during phagocytosis were comparable to controls in all patient groups. Slight, but significant, differences were found in chemotactic responsiveness of untreated patient groups when compared to controls. In almost all instances, chemotactic responsiveness reverted to normal in most patients studied after therapy for the malignant process. In patients with intact immunologic function these minor differences in chemotactic responsiveness are probably not sufficient to predispose to infection. However, this defect could be additive, and when present in combination with impaired immunity may contribute to compromised host defense.
Adolescent↗
Chemotactic deactivation of human neutrophils: possible relationship to stimulation of oxidative metabolism.
Neutrophils preexposed to high concentrations of activated complement or synthetic N-formyl methionyl peptides are inhibited in their subsequent spontaneous and chemotactic migratory responses. We have considered the possibility that a part of this nonspecific loss of migratory function may be attributable to the interaction of the leukocytes with reactive forms of oxygen deriving from the cytotaxin-induced burst of oxidative metabolic activity. For these studies we have assessed the effect of preexposure of neutrophils from patients with chronic granulomatous disease to cytotaxins on their subsequent migratory responses. We find that these responses are not altered by preexposure to either cytotaxin. Thus, there appears to be a functional relationship between deactivation and the ability of the normal neutrophil to undergo a cytotaxin-induced respiratory burst.
Blood↗
Chemotactic deactivation of human neutrophils: evidence for nonspecific and specific components.
Human polymorphonuclear neutrophils have been preexposed to activated complement as zymosan-activated serum (ZAS) or to the chemotactic oligopeptide N-formyl methionylphenylalanine (F-Met-Phe). Spontaneous migration and chemotactic responses toward the deactivating and other cytotaxins were monitored after washing and resuspension of cells in cytotaxin-free medium. Two patterns of deactivation were observed. Preexposure of the leukocytes to high doses of ZAS or F-Met-Phe decreased all subsequent migratory responses. Preexposure of the leukocytes to lower doses of ZAS or F-Met-Phe decreased only a subsequent chemotactic response to the deactivating cytotaxin. These results suggest two mechanisms, or components, of chemotactic deactivation.
Cell Movement↗