Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis

• Published in: Reproduction (Cambridge, England) Vol. 143; no. 5; pp. 651 - 662
• Main Authors: Guazzone, V A, Jacobo, P, Denduchis, B, Lustig, L
• Format: Journal Article
• Language: English
• Published: England BioScientifica 01-05-2012; BioScientifica Ltd
• Subjects: adhesion; Animals; antigens; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmunity; blood flow; CC chemokine receptors; CCL3 protein; CCR1 protein; CCR5 protein; CD49d antigen; cell adhesion; Cell adhesion molecules; Cell Adhesion Molecules - metabolism; Cell surface; Cells, Cultured; chemoattractants; Chemokine CCL3 - metabolism; Chemokine receptors; chemokines; Chemokines - metabolism; Chemotactic factors; chemotaxis; Chemotaxis, Leukocyte; Cytokines; Data processing; Disease Models, Animal; Endothelial cells; Endothelial Cells - immunology; Evolution; Germ cells; histopathology; Immune privilege; Immunization; Infection; Inflammation; Inflammatory diseases; Leukocyte migration; Leukocytes; Lymph nodes; Macrophages; Macrophages - immunology; Male; Molecular modelling; Monocytes; Orchitis; Orchitis - immunology; Orchitis - pathology; Peripheral blood; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Rats; Rats, Sprague-Dawley; receptors; Receptors, CCR1 - metabolism; Receptors, CCR5 - metabolism; Receptors, Chemokine - metabolism; recruitment; Testes; Testis - immunology; Testis - pathology; Time Factors; Trauma; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1470-1626; 1741-7899
• DOI: 10.1530/REP-11-0079

The testis is considered an immunologically privileged site where germ cell antigens are protected from autoimmune attack. Yet in response to infections, inflammatory diseases, or trauma, there is an influx of leukocytes to testicular interstitium. Interactions between endothelial cells (EC) and circulating leukocytes are implicated in the initiation and evolution of inflammatory processes. Chemokines are a family of chemoattractant cytokines characterized by their ability to both recruit and activate cells. Thus, we investigated the expression of CCL3, its receptors, and adhesion molecules CD31 and CD106 in an in vivo model of experimental autoimmune orchitis (EAO). In EAO, the highest content of CCL3 in testicular fluid coincides with onset of the disease. However, CCL3 released in vitro by testicular macrophages is higher during the immunization period. The specific chemokine receptors, CCR1 and CCR5, were expressed by testicular monocytes/macrophages and an increased number of CCR5+ cells was associated with the degree of testicular lesion. EC also play an essential role by facilitating leukocyte recruitment via their ability to express cell surface adhesion molecules that mediate interactions with leukocytes in the bloodstream. Rats with EAO showed a significant increase in the percentage of CD31+ EC that upregulate the expression of CD106. The percentage of leukocytes isolated from peripheral blood and lymph nodes expressing CD49d (CD106 ligand) also increases during orchitis. These data suggest that cell adhesion molecules, in conjunction with chemokines, contribute to the formation of a chemotactic gradient within the testis, causing the leukocyte infiltration characteristic of EAO histopathology.