Lymph node (but not spleen) invasion by murine lymphoma is both CD44- and hyaluronate-dependent.
Similar to activated T cells, LB T cell lymphoma expresses the CD44 cell surface Ag. In addition, the vast majority of LB cells also express the beta 2 (CD18) and alpha L (CD11a) chains of LFA-1 integrin. In view of the finding that anti-CD18 mAb blocked spleen, but not lymph node invasion by LB cells inoculated s.c. into BALB/c mice, we tested the ability of anti-CD44 mAb (IM 7.8.1) to block the infiltration of LB cells into the lymph nodes. We found that, as opposed to anti-CD18 mAb, anti-CD44 mAb, as well as its F(ab')2 or Fab fragment, prevented lymph node infiltration but had no effect on spleen invasion. This conclusion was based on histologic examination and [3H]thymidine incorporation into proliferating LB cells invading the lymphoid organs. Histologic analysis further demonstrated that LB cells invade the lymph node via the afferent lymphatics. The surface expression of CD44 molecules on LB cells was enhanced after PMA activation. PMA activation also enabled in vitro binding of the lymphoma to hyaluronic acid (HA), a known ligand of CD44. Because anti-CD44 mAb, its F(ab')2 or Fab fragment, and hyaluronidase blocked this binding, we also tested the ability of the enzyme to inhibit lymph node invasion by LB cells. We established through histologic examination and [3H]thymidine incorporation that hyaluronidase protected the lymph node, but not the spleen, from invasion by the lymphoma.
Zahalka
M A
MA
Lautenberg Center for General and Tumor Immunology, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Okon
E
E
Gosslar
U
U
Holzmann
B
B
Naor
D
D
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000032:analysis* / Q000276:immunology; D006821:Hyaluronoglucosaminidase / Q000502:physiology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology; D009368:Neoplasm Transplantation; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000032:analysis* / Q000276:immunology; D013160:Splenic Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D007140:Immunoglobulin Fab Fragments; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase