Sema7A is crucial for pulmonary defense against Klebsiella-induced pneumonia. In a murine model of bacterial-induced lung injury, 4 × 10⁷ gram-negative K pneumoniae was administered by intratracheal instillation directly into the lungs of WT and Sema7A^−/− mice. Measurements of PMN counts on the endothelial surface (A), in the interstitial space (B), in the BAL (C), and PNC numbers (D) per tissue section (magnification, 1000×) 24 hours after Klebsiella instillation in histological lung sections of WT and Sema7A^−/− mice (n = 3 per group on 3 different layers). The proinflammatory cytokines TNF-α (E), IL-6 (F), IL-1β (G), and myeloperoxidase activity (H) within the BAL of WT and Sema7A^−/− mice. (I) Histological sections demonstrating the quantity of Klebsiella, the alveolar inflammation (H&E staining), and PNC debris (PNC-specific staining) 24 hours after instillation (scale bar, 50 μm; magnification, 1000×). Colony forming units in BALF (J) and blood (K) taken 24 hours after Klebsiella instillation and incubated on nutrient agar plates for 24 h. (L) Representative images of cultured bacteria and (M) counts per tissue sections of K pneumoniae. (N) Representative images of H&E stained sections focusing on lung tissue injury 24 hours after Klebsiella instillation. (scale bar, 50 μm; magnification, 1000×). (O) Thickness of alveolar wall in tissue sections of WT and Sema7A^−/− mice 24 hours after K pneumoniae instillation (n = 3 per group; 10 random fields of view per mouse). (P) Survival curves of WT and Sema7A^−/− animals after the instillation of 4 × 10⁷ cells of K pneumoniae (n ≥ 6 per group). Group comparisons were performed by unpaired 2-tailed Student t tests; the data are the mean ± SD. For statistical comparisons of survival, the Gehan-Breslow-Wilcoxon test and the log-rank (Mantel-Cox) test were performed. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 as indicated. (Q) Schematic drawing of the role of Sema7a in pulmonary infection and defense. In pulmonary hemostasis, Sema7A is expressed on neutrophils and other tissues (left). During pulmonary infection Sema7A gains pathophysiological importance. Sema7A binds to Plexin C1, activates neutrophils, and increases the expression of integrins and L-selectin on their surface. This is important for a coordinated immunological response and the defense of the lung. BALF, bronchoalveolar fluid; H&E, hematoxylin-eosin; IL-6, interleukin-6.