Search

Adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are expressed in the kidney and are regulated by proinflammatory cytokines. These adhesion molecules play an important role in the binding and activation process of leukocytes and are of importance in inflammatory kidney diseases. This review article describes current knowledge regarding the structure, expression, and functional role of adhesion molecules and their significance in immune-mediated renal diseases.

Very Late Antigen-6 (VLA-6) is a laminin receptor found on T cells, macrophages and platelets and may function as an activation antigen. Here we describe that two monoclonal antibodies (mAb) targeting the VLA-6 alpha-chain are capable of inducing homotypic aggregation of murine T-cell lines (3A9 and C10 cells). 3A9 and C10 cells are of the memory phenotype (CD4+, CD8-, CD44+, CD45+) and express VLA-6 abundantly. The VLA-6-induced aggregation is temperature dependent, energy requiring, and involves the cytoskeleton. In addition, divalent cations (Ca2+ and Mg2+) are also necessary for aggregation. The VLA-6-induced aggregation is not inhibited with mAb targeting the LFA-1/ICAM-1, VLA-4/VCAM-1 and CD2/LFA-3 adhesion pairs. We conclude that VLA-6 has a broader function and can serve as an activation molecule, triggering homotypic aggregation of T-cell subsets.

Rat renal medullary tubular cells, prepared by collagenase dispersion and hypotonic lysis, were introduced in Teflon chambers for superfusion. Prostaglandin (PG) E2 and cyclic adenosine 5'-monophosphate (cAMP) production was measured in the effluent. Arginine vasopressin (AVP) but not 1-deamino-8-D-arginine vasopressin (dDAVP) (10(-10)-10(-6) M), induced a dose-dependent increase in PGE2 synthesis, whereas AVP and dDAVP produced a similar dose-dependent increase in cAMP synthesis. The Ca2+ ionophore A23187 (10(-6) M) stimulated PGE2 synthesis but not cAMP production. In contrast, forskolin (10(-5) M) stimulated cAMP synthesis without affecting PGE2 generation. The pressor antagonists dEt2AVP and d(CH2)5Tyr(Me)AVP (10(-5) M) completely inhibited the PGE2 response to 10(-8) M AVP, whereas d(CH2)5-D-LeuVAVP (10(-6) M), a mixed pressor-antidiuretic antagonist, inhibited incompletely. dEt2AVP did not significantly affect cAMP synthesis in response to 10(-8) M AVP, whereas d(CH2)5-D-LeuVAVP, and unexpectedly also d(CH2)5Tyr(Me)AVP, were inhibitory. dPTyr(Me)AVP (10(-7) M), a pressor antagonist, had an unexpectedly high cAMP-stimulating capacity. In Ca2+-free media containing EGTA, the PGE2 response to AVP and A23187 was inhibited. Nifedipine (10(-6) M) did not significantly inhibit the AVP-stimulated PGE2 production. Thus AVP-stimulated PGE2 synthesis is linked to a V1-receptor in renal medullary tubular cells and occurs independently to the activation of adenylate cyclase through a V2-receptor.

A superfusion technique was adapted to collagenase-dispersed renal medullary and cortical tubular cells to study prostaglandin (PG) synthesis in response to arginine vasopressin (AVP), angiotensin II (ANG II), bradykinin (BK), Ca2+ ionophore A23187, and to changes in osmolality. Medullary and cortical cells promptly responded to the stimuli by an increase in PGE2 and PGF2 alpha production, whereas 6-keto-PGF1 alpha was not detected. AVP and BK were active on medullary cells, and ANG II was active mainly on cortical cells. A23187 stimulated PG synthesis in both cells but predominantly in the medulla. PG synthesis was dependent on the presence of extracellular Ca2+. The Ca2+ entry blocking agents verapamil and lanthanum did not inhibit the PG response to AVP, BK, and ANG II. Thus peptide hormone-stimulated PG synthesis in renal tubular cells did not depend on Ca2+ influx through channels blocked by these agents. Hyperosmolar NaCl or mannitol stimulated PG synthesis in cortical and, more markedly, in medullary cells. Hyperosmolar urea inhibited PGE2 synthesis stimulated by peptide hormones, NaCl, and A23187 in both cell preparations. In conclusion, the superfusion of isolated tubular cells is a useful method to study the dynamic aspects of renal PG release in response to various sequentially applied stimuli.