Semaphorin 3A (
sema3A) belongs to the sub-family of the immune
semaphorins that function as regulators of immune-mediated
inflammation.
Sema3A is a membrane associated molecule on T regulatory cells and on B regulatory cells. Being transiently ligated to the cell surface of these cells it is suggested to be a useful marker for evaluating their functional status. In earlier studies, we found that reduced
sema3A concentration in the serum of
asthma patients as well as reduced expression by Treg cells correlates with
asthma disease severity. Stimulation of Treg cells with recombinant
sema3A induced a significant increase in FoxP3 and
IL-10 expression. To find out if
sema3A can be of benefit to
asthma patients, we evaluated the effect of
sema3A injection in a mouse model of
asthma. BALB\c-mice were sensitized using
ovalbumin (OVA) + adjuvant for 15 days followed by OVA
aerosol inhalation over five consecutive days. Four hours following air ways sensitization on each of the above days- 15 of these mice were injected intraperitoneally with 50 μg per mouse of recombinant human sema3A-FR and the remaining 15 mice were injected with a similarly purified vehicle. Five days later the mice were sacrificed, broncheo-alveolar lavage (BAL) was collected and
formalin-fixed lung biopsies taken and analyzed. In
sema3A treated mice, only 20% of the bronchioles and arterioles were infiltrated by inflammatory cells as compared to 90% in the control group (p = 0.0079). In addition, eosinophil infiltration was also significantly increased in the control group as compared with the
sema3A treated mice. In
sema3A treated mice we noticed only a small number of mononuclear and neutrophil cells in the BAL while in the control mice, the BAL was enriched with mononuclear and neutrophil cells. Finally, in the control mice, angiogenesis was significantly increased in comparison with
sema3A treated mice as evidenced by the reduced concentration of microvessels in the lungs of
sema3A treated mice. To conclude, we find that in this
asthma model,
sema3A functions as a potent suppressor of
asthma related
inflammation that has the potential to be further developed as a new therapeutic for the treatment of
asthma.