Neutrophil influx into the extravascular compartments of the lungs is a defining characteristic of the Acute Respiratory Distress Syndrome (ARDS). 1 During ARDS, circulating neutrophils become primed, resulting in reduced deformability and retention within the pulmonary capillary bed 2 3 followed by migration across the endothelium, through the interstitium and across the epithelium into the airspaces. 4 As neutrophils migrate, they may become activated to phagocytose invading pathogens and release oxidants, proteases and neutrophil extracellular traps, all of which play a role in killing pathogens. Although neutrophils may migrate into the airspaces without inducing an increase in protein permeability under certain conditions, 5 in ARDS neutrophils and their toxic mediators can cause tissue injury, including an increase in lung epithelial and endothelial permeability 6–9 which leads to the influx of protein-rich alveolar oedema and arterial hypoxaemia. 10 In fact, mortality from ARDS correlates with the extent of neutrophilia in the lung. 1 Treatment for ARDS is mainly supportive, consisting of low tidal volume ventilation and fluid restriction, approaches which have substantially improved outcomes. However, to further improve outcomes, specific therapies to limit inflammatory lung injury while preserving host defense are needed. Therefore, it is critical that we understand the mechanisms regulating neutrophil recruitment, priming, activation and effector functions. Leucocyte chemokines are classified into several families based on the position of cysteine (C) residues: CXC, CC, C and CX3C. 11 Neutrophil migration has classically been thought to be driven by the CXC chemokines, with CXCL8 (interleukin 8) in humans and its orthologs CXCL1 (KC) and CXCL2 (MIP2) in mice being the prototypical neutrophil chemokines. 12 CXC chemokines are elevated in patients with ARDS 13 and animal models of lung injury, 7 12 and CXCL8 levels are predictive of disease development, 14 severity 15 and mortality. 16 However, although CXC chemokines are responsible for much of the neutrophil recruitment to the lungs during lung injury, blockade of CXCL8 or CXCL1/2 prevents some but not all neutrophil recruitment. 7 12 Additional CXC chemokines such as CXCL5 (LIX/ENA-78), CXCL12 (SDF-1) and CXCL15 (lungkine), as well as other mediators such as LTB4 and C5a, also are neutrophil chemoattractants. 8 Chambers et al have previously published elegant animal studies demonstrating that the CC chemokines CCL2 (MCP-1) and CCL7 (MCP-3), classically chemotactic for monocytes, 11 contribute to neutrophil recruitment in acute lung injury. After challenge with lipopolysaccharide (LPS) or live bacteria, CCL2 and CCL7 were rapidly upregulated in the lungs, the CC chemokine receptors CCR1 and CCR2 were expressed on neutrophils, and blockade of CCL2 and/or CCL7 attenuated neutrophil recruitment. 17 18 In Thorax, Williams et al 19 tested their experimental findings in patients, asking whether CCL2 and CCL7 are similarly important in neutrophil recruitment in ARDS. Both CCL2 and CCL7 were elevated in the bronchoalveolar lavage (BAL) fluid of patients with ARDS and the neutrophil chemotactic activity of BAL fluid was as much attributable to either CCL2 or CCL7 as to CXCL8. Although CCL2 and CCL7 were weaker neutrophil chemoattractants than CXCL8 when chemotaxis towards recombinant chemokines was tested, CCL2 and CCL7 each significantly enhanced neutrophil chemotaxis to CXCL8, suggesting that the effect is synergistic. Finally, their studies demonstrated that the CXC chemokine receptor CXCR1 was downregulated while the …