Haptoglobin is a natural regulator of Langerhans cell function in the skin.
Langerhans cells (LC), the best-understood antigen presenting cells (APC) of the skin, are functionally plastic. Freshly obtained LC readily activate allogeneic T cells, but are incapable of activating autologous, naive T cells. When placed in culture in the presence of GM-CSF, LC up-regulate surface expression of class I and II MHC molecules along with co-stimulatory molecules, such as B7, CD40 and IL-12. This functional transformation enables the cells to activate naive, autologous T cells in vitro. It is paradoxical that intracutaneous administration of exogenous GM-CSF fails to induce intraepidermal LC to undergo functional transformation in situ. It has been reported that serum contains a factor that prevents fresh LC from undergoing functional transformation in culture, and the relevant serum factor has now been identified as haptoglobin (Hp), based on the following experimental results: (a) SDS-PAGE, amino acid sequencing, and mass spectrometric analyses of the inhibitory factor purified by high performance liquid chromatography (HPLC) from normal human serum revealed molecules completely homologous to Hp alpha-1 chain; (b) pure human Hp, but not serum depleted of Hp, inhibited fresh LC from acquiring the capacity to activate autologous T cells in vitro; (c) abundant Hp was detected in cytoplasmic compartments of fresh, but not cultured, LC. It was concluded that Hp, an acute phase protein, is a systemically-derived factor that prevents epidermal LC from spontaneously undergoing functional maturation in the skin. This novel property of Hp may be important in ameliorating or preventing certain T cell-dependent inflammatory skin diseases.
Xie
Y
Y
Schepens Eye Research Institute, 20 Staniford St., Boston, MA, 02114, USA.
Li
Y
Y
Zhang
Q
Q
Stiller
M J
MJ
Wang
C L
CL
Streilein
J W
JW
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006242:Haptoglobins / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007801:Langerhans Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes
D006242:Haptoglobins