Identification of human cysteine-rich secretory protein 3 (CRISP-3) as a matrix protein in a subset of peroxidase-negative granules of neutrophils and in the granules of eosinophils

Journal of Leukocyte Biology

Ole E. Sørensen¹  Niels Borregaard¹  Lars Kjeldsen¹  Jero Calafat²  Lene Udby¹ 

[1] Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark; and Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark; and Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark; and;Department of Cell Biology, The Netherlands Cancer Institute, Amsterdam Department of Cell Biology, The Netherlands Cancer Institute, Amsterdam Department of Cell Biology, The Netherlands Cancer Institute, Amsterdam

关键词: specific granules;    gelatinase granules;    SGP28;    immunogold electron microscopy;    subcellular fractionation;    granulocytes;   

DOI  :  

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) was originally discovered in human neutrophilic granulocytes. We have recently developed a sensitive sandwich enzyme-linked immunosorbent assay for CRISP-3 and demonstrated the presence of CRISP-3 in exocrine secretions. To investigate the subcellular localization and mobilization of CRISP-3 in human neutrophils, we performed subcellular fractionation of resting and activated neutrophils on three-layer Percoll density gradients, release-studies of granule proteins in response to different secretagogues, and double-labeling immunogold electron microscopy. CRISP-3 was found to be localized in a subset of granules with overlapping characteristics of specific and gelatinase granules and mobilized accordingly, thus confirming the hypothesis that peroxidase-negative granules exist as a continuum from specific to gelatinase granules regarding protein content and mobilization. CRISP-3 was found to be a matrix protein, which is stored in granules as glycosylated and as unglycosylated protein. The subcellular distribution of the two forms of CRISP-3 was identical. In addition, CRISP-3 was found as a granule protein in eosinophilic granulocytes. The presence of CRISP-3 in peroxidase-negative granules of neutrophils, in granules of eosinophils, and in exocrine secretions indicates a role in the innate host defense.

【 授权许可】

Unknown