Langerhans cells (LC) are bone marrow-derived, immunocompetent cells which comprise 2-6% of the human epidermal cell population. Although these cells have been implicated as playing a major role in contact dermatitis, probably by acting as antigen presenting cells, their exact function(s), in particular their secretory products, is not understood. Moreover, although their numbers are altered in a variety of skin diseases, e.g. lichen planus, mycosis fungoides, AID, their role (if any) in these disorders is totally obscure. The experiments proposed in this grant have two major goals: 1) to define the products produced and secreted by LC in short term cultures and to determine which substances influence this production. In particular, supernatants from LC cultures will be assayed for prostaglandin E2, interleukin-1, interleukin-2, tumor necrosis factor and enkephalin; 2) the cells will be assayed for the presence of mRNAs for interleukin-1 and tumor necrosis factor; 3) to establish long term cultures of """"""""pure"""""""" LC. These cells will be used to determine whether human LC indeed are antigen presenting cells (e.g. in contact dermatitis). Furthermore, if, as our preliminary results indicate, LC do not express Birbeck granules, experiments will be performed to detect and characterize a possible keratinocyte-generated factor which induces these granules.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
7R01AR038658-04
Application #
3158707
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1990-09-16
Project End
1992-03-31
Budget Start
1990-09-28
Budget End
1991-03-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Sri International
Department
Type
DUNS #
City
Menlo Park
State
CA
Country
United States
Zip Code
94025
Morhenn, V B; Waleh, N S; Mansbridge, J N et al. (1994) Evidence for an NMDA receptor subunit in human keratinocytes and rat cardiocytes. Eur J Pharmacol 268:409-14
Morhenn, V B; Lee, S W; Ilnicka, M et al. (1992) Activated human Langerhans cells express mRNA for IL-1 alpha and IL-1 beta and produce these cytokines but do not secrete them. Cytokine 4:500-5
Lee, S W; Morhenn, V B; Ilnicka, M et al. (1991) Autocrine stimulation of interleukin-1 alpha and transforming growth factor alpha production in human keratinocytes and its antagonism by glucocorticoids. J Invest Dermatol 97:106-10
Neely, E K; Morhenn, V B; Hintz, R L et al. (1991) Insulin-like growth factors are mitogenic for human keratinocytes and a squamous cell carcinoma. J Invest Dermatol 96:104-10
Morhenn, V B (1990) Pemphigus: an alternative approach to treatment. Arch Dermatol 126:1238