Abstract
Purpose: :
Annexin-A1 (Anx-A1) is a glucocorticoid-regulated 37kDa protein with powerful anti-inflammatory actions: enhanced release from target cells occurs following addition of the anti-allergic cromone drugs. Anx-A1 is inactivated by proteolytic cleavage of the N-terminus and increased amounts of the cleaved 33kDa product correlate with inflammatory responses. We investigated if Anx-A1 is detectable in human tear specimens from patients with vernal keratoconjunctivitis (VKC).
Methods: :
Tear specimens were collected from patients with VKC (n=23), and non-inflammatory control tear specimens from healthy volunteers (n=17) who gave informed consent. Anx-A1 protein levels were measured by ELISA and by Western blotting.
Results: :
In cell-free tear specimens from healthy donors, the concentration of Anx-A1 was 433.6 ± 54.3 pg/ml (n=17) and >90% was in the intact form. In tears from VKC patients however, total Anx-A1 increased to 1908 ± 319.3 pg/ml (n=23; p<0.05) but only 48% (921.5 ± 193.5 pg/ml) of this was the intact biologically active species. Proteolytic cleavage of the protein was reduced in the group treated with Lodoxomide (>80% is intact form, n=11, p<0.01).
Conclusions: :
Anx-A1 is constitutively present in normal human tears and is proteolytically cleaved to inactivation during chronic allergic disease. Lodoxomide treatment decreased the level of cleaved protein in VKC patients, and this is perhaps related to its therapeutic action.
Keywords: conjunctivitis • inflammation • pathology: human