Naslov
A monoclonal antibody (MAb) to CD44 mediates the expansion of CD34^+ progenitor cells in canine long-term marrow culture (LTMC)

Autori
Križanac-Bengez, Ljiljana ; McSweeney, Peter A. ; Santos, Erlinda B. ; Sandmaier, Brenda M.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum Biologorum 99 (suppl. 2), 1997 Annual Meeting of the Croatian Immunological Society / Vitale, Branko ; Rabatić, Sabina - Zagreb : Hrvatsko prirodoslovno društvo, 1997, 11-11

Skup
1997 Annual Meeting of the Croatian Immunological Society

Mjesto i datum
Zagreb, Hrvatska, 06.11.1997. - 07.11.1997

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
adb2; CD44; CD4; cell adhesion molecules; long-term marrow culture

Sažetak
Monoclonal antibody (MAb) S5 recognizes the CD44 marker of hematopoietic cells. If infused into recipient dogs before total body irradiation and transplantation, it facilitates engraftment of MHC-mismatched marrow. To understand the mechanism of S5 action, S5 and two other anti-CD44 MAbs (IM7, H1) were investigated in vitro. None of the three MAbs affected the clonal growth of unfractionated marrow cells, however all enhanced CFU-GM production of sorted CD34^5 cells. Enhancement was abrogated by the anti-CD18 MAb, 60.3. In the long-term culture-initiating cell assay (LTC-IC), pretreatmnet of the stromal layer with S5 stimulated the CFU-GM production if the cultures were seeded with whole allogeneic bone marrow cells but not with CD34^+ sorted cells. This suggested that the effect of S5 on CFU-GM production was mediated through accessory cells influenced by the S5-pretreated stroma. That idea was supported by the observation that S5 induced a 2-10 fold increase of the number of CD14^+ cells in the adherent layer of LTMC, as compared to untreated control cultures and to the cultures treated with other anti-CD44 MAbs. S5 was the only anti-CD44 MAb that increased the production of CD34^+ cells in the adherent layer of the LTMC. That occured 1-2 weeks after the initiation of the cultures and preceded the increase in CFU-GM production in the nonadherent compartment after week 2. In addition, S5 increased the production/maturation of T (NK) cells from the 3rd week on. The development of lymphoid cells in untreated canine LTMC before that time is rather low. The stimulatory effect of S5 on the CFU-GM and the cytotoxic T (NK) cell populations was completely abrogated by anti-CD18 (b2-integrin) MAb 60.3. Therefore, the expression of adhesion molecules (CD44, VLAa4, ICAM-1, L-selectin, CD18, CD11a-c, adb2) was investigated. S5 consistently increased the production of cells expressing the b2 integrin adhesion molecule adb2 in the adherent layer of the LTMC while no change was observed in the expression of other b2 integrins. adb2 is expressed on tissue macrophages (CD14^+) and on a subset of lymphoid cells, but its function is unknown. Our data suggest that S5 enchances the engraftment of bone marrow cells in vivo by a mechanism related to the changes in the accessory cell compartment of the stromal layer resulting in an increase of CD34^+cell production. The effect is partly mediated through a CD18 (b2) pathway, possibly through adb2.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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