Effects of bone marrow reconstitution with WT cells in WT and PPT-A gene–deleted (PPT-A^–/–) mice and with PPT-A^–/– cells in WT mice on immune complex–mediated lung injury. (a) WT mice reconstituted with WT bone marrow after conditioning irradiation. (b) PPT-A^–/– mice (shown by crossing of cells affected by the gene deletion) reconstituted with WT bone marrow, restoring the ability of their hemopoietic cells to produce substance P (SP) and other PPT-A gene–encoded neurokinins. (c) WT mice reconstituted with PPT-A^–/– bone marrow, eliminating the ability of their hemopoietic cells to produce PPT-A gene–encoded neurokinins. (d) WT mice reconstituted with WT bone marrow (n = 12) developed intense inflammation after immune complex formation. Reconstitution of PPT-A^–/– mice with WT bone marrow did not reestablish the inflammatory response (n = 15; P < 0.0001). Reconstitution of WT mice with PPT-A^–/– bone marrow protected against this response (n = 15; P < 0.0001). Cell counts and Evans blue ratios are shown in comparison with control mice injected intravenously with ovalbumin and intratracheally with normal saline (white bars; n = 4 WT bone marrow to WT, 6 PPT-A^–/– bone marrow to WT, and 3 WT bone marrow to PPT-A^–/– mice). TNF-α levels were determined in fewer mice (n = 7, 10, and 12, respectively). Values are shown as mean ± SE, except for TNF-α levels, which are shown as median and 25th to 75th percentile span.